Discussion Guide — Chapter 25

Six prompts, with what to listen for. Each runs 8–12 minutes.

Prompt 1. "1.27 million or 4.95 million — which is the death toll of antibiotic resistance?"

Listen for: students who notice that the question is malformed before you tell them. The productive answer is that both numbers are correct measurements of different things, and that the question fails by not specifying which. Weak answers pick one and defend it. Push anyone who says one figure is "wrong" — neither is. Close by asking what the equivalent distinction would be for a claim about a peptide's benefit: attributable to the drug, or merely observed alongside it?

Prompt 2. "Bacteria have been exposed to antimicrobial peptides for hundreds of millions of years and these peptides still work. Doesn't that prove resistance can't evolve?"

Listen for: the move from evidence of slowness to a claim of impossibility. Strong students will point out that innate immunity operates under conditions a drug cannot reproduce — brief, local, compartmentalized, cooperative exposure — so the evolutionary track record may not transfer to sustained systemic dosing. That is the sophisticated version and it is worth drawing out. Also listen for anyone who raises mcr unprompted. Close by asking what evidence would be needed to show that AMP resistance is genuinely slower to emerge in clinical use — and note that we cannot currently collect it, because there is no systemic AMP in clinical use to observe.

Prompt 3. "Two peptides have the same MIC. One has a selectivity index of 64, the other 4. Which discovery would get the press release?"

Listen for: recognition that the press release writes itself from the MIC alone and that the disqualifying number is not in the antibacterial data at all. Push toward the general principle: the number that kills a program is often not the number the field advertises. Ask students to name the equivalent hidden number in another domain they know — bioavailability, dropout rate, absolute versus relative risk reduction. Close by asking what a responsible press release for the second peptide would say.

Prompt 4. "How many antimicrobial peptides are currently approved as drugs?"

Listen for: the guess. Most classes say zero, one, or two. Let the guesses stand before revealing colistin, daptomycin, vancomycin, polymyxin B, bacitracin, and gramicidin. Then ask the important question: why did you think the answer was zero? The productive answers implicate the sources students have been reading — coverage that uses "antimicrobial peptide" to mean specifically the host-defense-peptide research program, and then reports that program's lack of an approved systemic agent as though it described the whole category. This is the chapter's best moment for teaching source skepticism, because students catch themselves rather than being told.

Prompt 5. "Colistin is rated ✅ and it causes kidney injury. Defend that rating."

Listen for: the separation of "the evidence supports this claim" from "this is a good drug." Expect resistance; some students will find the rating actively misleading. Take the objection seriously and then ask what the alternative would be — a rating system that downgrades effective drugs for being unpleasant would rate most of oncology ❌. Draw out the denominator argument: the comparison in 1980 was against an aminoglycoside; the comparison in 2015 was against an untreated infection. Close by asking what single sentence they would add to a consumer-facing summary so ✅ is not misread — and note that the book's answer is to state the toxicity in the same breath as the rating, which is what §25.8 does.

Prompt 6. "Is 🔬 an honest rating or a way of avoiding a judgment?"

Listen for: the criterion. The answer the chapter wants is that 🔬 is honest exactly when it names what would resolve it, in both directions, with enough specificity to be checkable — and evasive otherwise. Push students who say "it depends on intent"; intent is unobservable, and the test has to be a property of the written rating. Then apply it: read out a 🔬 with the resolving line removed and ask whether it is a rating. Close by asking where else students have seen "more research is needed" doing the work of a conclusion, and whether they can now say what was missing from it.